ArticleJournal of veterinary internal medicine2026
Development and pilot testing of U1 Adaptor therapy targeting SOD1 expression for dogs with degenerative myelopathy.
Article in Journal of veterinary internal medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
backgroundDegenerative myelopathy (DM) is a progressive neurodegenerative disease in dogs associated with a superoxide dismutase 1 (SOD1) gene mutation, resulting in SOD1 protein aggregation within neurons and astrocytes. Targeting SOD1 expression represents a viable therapeutic strategy. HYPOTHESIS/
objectivesAssess the safety and potential efficacy of SOD1 silencing by intrathecal administration of a U1 Adaptor oligonucleotide targeting canine SOD1 (U1cSOD1) in healthy and DM-diseased dogs. ANIMALS: Seven purpose-bred healthy adult dogs, 1 dog with stage III DM and 4 dogs with Stage I DM.
methodsHealthy dogs and the stage III DM dog received a single intrathecal dose of U1cSOD1 or a vehicle and were euthanized 5 or 30 days later. Four stage I DM-affected dogs received monthly intrathecal injections of U1cSOD1 for up to 10 months. Physical and neurologic examinations, blood tests, cerebrospinal fluid analysis, as well as pharmacokinetic, pharmacodynamic, and histopathologic analyses were performed in all dogs.
resultsIn dogs receiving U1cSOD1, spinal cord SOD1 RNA expression near the injection site was decreased to a median of 37% of normal (range, 21%-79%). Dogs tolerated the procedure and test agent well, exhibiting no adverse effects clinically or histopathologically. Two of 34 injections were aborted because of high intrathecal pressure. CONCLUSIONS AND CLINICAL IMPORTANCE: Monthly intrathecal injections of U1cSOD1 in DM-affected dogs are safe and decrease spinal cord SOD1 expression by >50% but an alternative administration route would be preferred. This first test of U1 Adaptor technology in dogs with a naturally occurring disease shows potential for therapeutic intervention in a fatal disease without a current cure.
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